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number of minute blood-vessels in this membrane.

If, on the other hand, the general systemic poisoning is
responsible for chorea one almost despairs of getting any
nearer the solution of this problem until the chemistry of
rheumatism is elucidated, for these general systemic poisonings
are beyond the reach of morbid anatomy. Working along
these lines we have attempted by intravenous injections of
formic acid in rabbits to produce choreiform movements, but
failed to obtain any such result. Reichart 27 has recently
published accounts of a careful investigation of two brains in



238 INVESTIGATIONS ON THE NERVOUS

cases of fatal chorea. The bacteriological investigations were
negative, but in both cases he found small haemorrhages
scattered irregularly throughout the brains ; there were
dilatation of blood-vessels and perivascular exudation of cells.
This observer also found fatty changes in the nerve fibres of
the brain and cord. These are changes such as would be
associated with an infection of the rheumatic type. The
finding of such local lesions to some extent supports the view
that chorea is a result of such changes rather than of a general
cerebral poisoning by the toxins. A more convincing point in
the pathology of chorea would be the demonstration of the
diplococci in the pia mater or brain in cases of chorea. Our
opportunities for doing this have been few. At a meeting of
the Pathological Society in December 1900 28 we demonstrated
diplococci in the motor cortex of a case of very severe chorea,
but most unfortunately we did not, when we made the necropsy,
recognise the relation of the diplococcus to rheumatism. In
both our recent cases alluded to here we found them in the
pia mater as we foretold from animal experiment in 1900 —
viz., in the neighbourhood of the capillary blood-vessels.
There is no doubt in our minds that the destruction of these
diplococci in the pia mater must be rapid, for chorea is
a lesion comparable to rheumatic arthritis in the tendency
to complete recovery, and, as we have already pointed out,
it is no easy task to find them in acute arthritis. It is,
we think, encouraging to have shown a diplococcus in
three consecutive cases of chorea and in the last case we
know that this diplococcus can produce arthritis and peri-
carditis in rabbits and could be isolated from the cerebro-
spinal fluid.

Lastly, a section of a mitral valve from a case of early
endocarditis with very severe chorea illustrates how easily
the brain could be infected from the blood stream, vide
Fig. 64. These have been our only opportunities and
neither of the last two cases should we have chosen for
demonstration, for they were not essentially cases of fatal
chorea but rather fatal pericarditis with chorea. During
the last five years we have never had an opportunity of
investigating one of the rare cases of fatal chorea. We
have not attempted lumbar puncture for we cannot persuade
ourselves to do this simply for purposes of investigation, and









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« FIG. 76

Film of the pia mater showing : A, diplococci in the pia mater ; B, a capillary
blood-vessel. From a case of fatal rheumatic pericarditis with chorea. (Zeiss,

Ohj. T \r, 0C. 12.)



MANIFESTATIONS OF ACUTE RHEUMATISM 239

our views upon the probability of success of this method are
expressed in our views upon arthritis. In spite of this, the
fact that we have succeeded in demonstrating the diplococcus
in cases in which death occurred with chorea does, we believe,
add another link to the chain of evidence, and it is the more
suggestive because we discovered them in the pia mater near
capillary blood-vessels in the rabbit which showed involuntary
movements. 29

These experimentally produced irregular movements need
a passing mention. Originally described by ourselves in 1900,
we then in a very guarded manner suggested that the move-
ments in the rabbit were analogous to chorea in a child. Meyer
and Beattie independently verified the occurrence and noticed
twitching movements. Cole later produced twitching move-
ments in rabbits by the injection of other streptococci and
states that the movements had no resemblance to chorea. In
our case the movements were of that type and entirely different
from convulsive movements or the twitchings of a dying
animal ; in fact, we killed the animal in order to demonstrate
the diplococci in the brain or pia mater. The search, it may
be added, was most tedious and difficult, as might be supposed
when it is remembered how minute is the size of this diplococcus.

To summarise, we believe that eventually rheumatic chorea
will prove to be a local infection of the nervous system and
that most of its symptoms are the result of a slight meningo-
encephalitis and possibly meningo-myelitis. Our reasons for
this belief are : (1) We have isolated and cultivated the
diplococcus from the cerebro-spinal fluid in four cases of fatal
rheumatism, in three of which there was chorea at the time of
death. (2) We have produced irregular movements, arthritis,
endocarditis, and pericarditis by intravenous injections of the
diplococcus into rabbits. (3) We have demonstrated the
presence of diplococci three times in the cerebral pia mater and
once in the brain from chorea. (4) We have demonstrated
them, in the brain and pia mater of the rabbit that had shown
the irregular movements.

Part III. — Rheumatic Meningitis (?)

Our last case is a most interesting one. A well-made and
intelligent boy, 13 years old, was admitted into University



240 INVESTIGATIONS ON THE NERVOUS

College Hospital on August 26, 1904, suffering from arthritis
of the ankles and knees and from pain across the chest upon
drawing breath. The first attack of pain had occurred four
days before his admission, the ankles had commenced to swell
three days before, and the knees upon the day previous. The
family history showed that the boy's father had suffered from
rheumatic fever but the patient himself, except for an attack
of measles and an operation for adenoids, had enjoyed excellent
health. His condition on admission appeared to be a very
ordinary attack of rheumatic fever. The temperature was
103. 6° F. and the arthritis was of the usual type, the heart
was dilated, and there was a definite systolic mitral murmur
which was conducted to the left axilla. Further, rest and
salicylate of sodium rapidly reduced the temperature and by
the 30th, that is in four days, all pain and swelling had dis-
appeared. From that date until September 17, a period of nearly
three weeks, his convalescence was uninterrupted, while in
order to prevent a relapse small doses of salicylate of sodium
were continued. On the 17th, without any apparent cause,
he complained of headache ; he was sick, and his temperature
rose to 102. 4 F. The next day, although better in the
morning, he again vomited in the afternoon and suffered severe
pain in his head. That evening he was drowsy and his tempera-
ture rose again to 102. 6° F. The bowels were constipated and
for this reason an enema was given, after which he collapsed
and became cyanosed and almost pulseless. At 8 a.m. on the
19th he became unconscious, with fixed dilated pupils and
general muscular rigidity, alternating with naccidity. His skin,
though hot, was moist ; his temperature in the axilla at 8 A.M.
was 101 F., and at n a.m. 102. 4 F. The temperature was
now taken in the rectum and also twice with different thermo-
meters in the groin and axilla. In the rectum the temperature
was 106. 4 F. ; in the other situations it was still 102. 4 F.
All efforts at treatment were fruitless and the boy died comatose
at 7.40 that evening. The difference in the temperature in the
axilla and in the rectum of over 4 F. is remarkable and we
believe very exceptional ; in fact, if the rectal temperature
had not been taken the hyperpyrcxial element in the illness
would certainly have escaped notice. The clinical aspect of
this case was a very puzzling one, not only on this account but
because the symptoms supervened without warning at a time







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MANIFESTATIONS OF ACUTE RHEUMATISM 241

when all believed the boy was quite convalescent. There are,
however, other cases on record in which the supervention of
cerebral rheumatism has been recorded during convalescence,
and it is well known that this condition may occur when the
first symptoms of rheumatism are slight as well as when they
are severe. The most probable diagnosis thus appeared to be
cerebral rheumatism.

The necropsy was made 15 hours after death. No changes
were found in the affected joints. There was a slight excess
of clear fluid in the pericardium and the mitral valve showed
early endocarditis in the process of healing. There was also
slight pleuro-pericarditis on the left side which was of recent
origin. These morbid changes, we would point out, were
entirely in accord with the occurrence of an attack of recent
acute rheumatism. In no part of the body could any focus of
suppuration be seen. Examination of the brain showed a
condition of meningitis almost entirely basal in distribution
and not suppurative. Except that it is spread further than is
usually the case in post-basic meningitis, the appearance was
almost identical with that condition. A good deal of turbid
fluid was present together with flakes of exudation over the
medulla, pons, and cerebellum. There was also a general spinal
meningitis. The films showed minute diplococci in numbers.
And we would point out that even in this extraordinary and
virulent case it was by no means easy to find the micrococci in
the pial tissues.

Cultures were taken from the blood in the heart, the peri-
cardial and cerebro-spinal fluids, and brain. The cultures
from the cerebro-spinal fluid contained a pure growth of a
diplococcus in bouillon milk and glycerine agar. The virulence
of these cultures was higher than is usually the case with the
diplococcus and two rabbits inoculated with large doses died
comatose within 24 hours. The blood film showed a minute
diplococcus which was capsulated. The diplococcus was
isolated from the blood of one and a small dose was injected
intravenously into a third rabbit. After showing some loss of
health this animal recovered. Return was made to the original
culture and again a large dose produced rapid death, but a
small dose was recovered from. After two months interval a
large dose was again used, with the result that the rabbit
developed arthritis of the shoulder joints and was killed in the

1G



242 INVESTIGATIONS ON THE NERVOUS

convalescent stage. The diplococcus was recovered from the
damaged joints.

This case was clinically and experimentally very exceptional
and we have only brought it forward as a contribution to the
subject of meningitis in the rheumatic. Had our paper been
brought forward in its original form we should have discussed
the various explanations of the case and the details of its
bacteriology, but to do so now would be out of place. We
bring it forward, however, because we are inclined to the belief
that it was a true rheumatic meningitis in spite of the fact that
we observed capsulation of the diplococci in the rabbit's blood,
which we admit has hitherto been regarded as a distinguishing
feature of the pneumococcus. In any case it is worthy of
record should others happen upon such a remarkable condition.
Lastly, if for the moment this case is accepted as a true
rheumatic meningitis the question arises as to how we are to
link together these three remarkable rheumatic lesions of the
brain termed (i) rheumatic chorea ; (2) rheumatic hyper-
pyrexia or cerebral rheumatism ; and (3) rheumatic meningitis.
In rheumatic hyperpyrexia the rule is that no gross macro-
scopical lesion is found. Of this we believe there is no doubt,
for we have referred to a number of such cases since the time
of Fuller and have again and again found the same record of
an absence of gross lesions. Nevertheless, recent research has
shown that there are very grave microscopical changes. Thus
Josue and Salomon 30 in 1903 found in such a case diplococci
in the pia mater and in some of the cerebral blood capillaries,
and demonstrated by Nissl's method profound changes in the
nerve cells of the frontal and motor cortex. In October of this
year Gandy and Borgnait Legneule 31 in a rapidly fatal case
found diffuse chromatolysis. To us, then, it appears that this
nervous lesion is an acute rheumatic toxaemia in contrast to the
multiple and slight local lesions we believe exist in chorea.
Rheumatic meningitis we would place between these two
lesions, because there is on the one hand profound poisoning
and on the other a severe local lesion. Are these nervous
lesions, it may be asked, in any way comparable to rheumatic
lesions of other organs ? We believe so, and would venture
the following comparison :

Mild rheumatic carditis and chorea.

Severe rheumatic pericarditis and rheumatic meningitis.



MANIFESTATIONS OF ACUTE RHEUMATISM 243

Acute fatal rheumatic cardiac dilatation and acute fatal
rheumatic hyperpyrexia.

REFERENCES

1 A paper read before the Neurological Society of the United Kingdom
on November 23, 1905.

2 The Lancet, September 22 and 29, 1900.

3 Klebs, Archiv fur Experimentelle Pathologie, 1875, Band IV, p. 469.
Wilson, Edinburgh Medical Journal, 1885, vol. xxx, p. 1105. Mantle,
" The Etiology of Rheumatism from a Bacterial Point of View," Brit.
Med. Jour., 1887. Popoff, Meditz Prebavlena k'Morskomu Sbomekie,
1887, p. 461. Von Leyden, Congress der Innere Medicin, Berlin, July 2,
1894. Triboulet and Coyon, Comptes Rendus de la Societe de Biologie,
1898, p. 214. Westphal, Wassermann, and Malkoff, Berliner Klinische
Wochenschrift, 1899, No. 29, &c.

4 Poynton and Paine, Transactions of the Royal Medical and
Chirurgical Society, 1902.

5 Transactions of the Fourteenth International Congress of Medicine,
Section of Medicine, 1903.

6 Vernon Shaw, Journal of Pathology and Bacteriology, December 1903.

7 Ainley Walker, Practitioner, 1903.

8 Beattie, Brit. Med. Jour., December 1904.

9 Loc. cit. 10 Loc. cit. n Loc. cit.

12 Predtetschensky, Vratch, 1901, No. 24.

13 Fritz Meyer, Deutsche Medicinische Wochenschrift, 1901.

14 Singer, V erhandlungen des Congresses fur Innere Medicin, 1897,
1899.

15 Allaria, Rivista Critica-de Clinica Medica, 1901, No. 47.

16 Jarvis, TMse de Paris, 1902.

17 Cole, Journal of Infectious Diseases, vol. i, No. 4, 1904.

18 Longcope, American Journal of the Medical Sciences, 1904.

19 Herry, La Semaine Medicate, October 4, 1905.

20 Philipp, Deutsches Archiv fur Klinische Medicin, Band LXX,
Hefte 1-3.

21 Walker and Ryffel, Brit. Med. Jour., September 19, 1903.

22 Gordon, Lancet, November 11, 1905, p. 1400.

23 Dana, American Journal of the Medical Sciences, 1894, p. 31.

24 Apert, Societe de Biologie, January 20, 1898.

25 Poynton and Paine, Transactions of the Fourteenth International
Congress of Medicine, Section of Pediatrics, 1903.

26 Poynton and Shaw, Transactions of the Pathological Society, 1904.

27 Reichart, Deutsches Archiv fur Klinische Medicin, 1902, p. 504.

28 Poynton and Paine, Transactions of the Pathological Society, 1901.

29 Poynton and Paine, " Some Further Investigations upon Rheumatic
Fever," Lancet, May 4, 1901, p. 1260.

30 Josue and Salomon at a meeting of the Paris Hospitals Medical
Society, July 25, 1905.

31 Gandy and Borgnait Legneule at a meeting of the Hospitals
Medical Society, Paris, October 27, 1905.



PAPER NO. XIX

A CONTRIBUTION TO THE PATHOLOGY
OF CHOREA

By Dr. F. J. POYNTOX and Dr. W. GORDON HOLMES
(Reprinted from the Lancet, October 13, 1906.)

The collaboration of Dr. Gordon Holmes, then Director of the Nervous
Disease Research Fund at the National Hospital for the Paralysed
and Epileptic, enabled us in this paper to study the minute pathology
of chorea by the most recent methods of that date. The number of cases
of fatal chorea that were investigated was increased and a detailed
explanation of the occurrence of rheumatic chorea given in the light of
the changes that were found in the nervous system. In addition, a
study of a case of chorea occurring in pregnancy enabled us to discuss
the nature of this condition, which, in accord with the experience of
other investigators, we believed to be frequently rheumatic in nature.

In the present communication we are, firstly, adding three
more to the recorded observations of the presence of a diplo-
coccus in the pia mater of cases that have proved fatal while
suffering from chorea. In addition, this micro-organism has
been demonstrated in the brains of these cases lying in the
perivascular spaces and connective tissue. Secondly, we have
also studied by the most recent methods the two series of
changes — viz., those affecting the connective and vascular
tissues and those which occur in the nervous tissues in chorea.
And, lastly, we have demonstrated that in a case of chorea
which occurred in a first pregnancy lesions were present
similar to those that were found in the rheumatic cases. Such
opportunities could never have offered themselves if it had not
been for the kindness of Sir Cooper Perry and Dr. H. S. French,
Dr. J. Rose Bradford and Dr. H. Batty Shaw, and we are
greatly indebted to them for the pathological material and
permission to use the clinical and post-mortem notes of these
cases. Deaths from chorea are so rare that the opportunities

244



PATHOLOGY OF CHOREA 245

for testing the results in several cases at short intervals
are most exceptional, but through their kindness these
three cases came to us within a month and gave us an
opportunity of repeating and comparing our observations.

The Clinical Cases

Case i. Our first case, for which we are indebted to
Dr. Shaw, was that of a girl aged seven years, who was
admitted to the Children's ward at University College Hospital
on March 25, 1906. Her illness had commenced three weeks
previously with multiple arthritis, ushered in with acute
malaise and vomiting. After a temporary improvement
chorea and pericarditis developed, and when admitted her
condition was hopeless. Death occurred two days later from
heart failure, the chorea having lasted about 17 days. While
under observation the temperature ranged between 104 and
99 F., the chorea was very severe, the pericarditis was general,
and valvular disease was also present. In her previous history
there was a record of an attack of rheumatic fever at five years
of age. The post-mortem examination showed general and
recent pericarditis, bilateral pleurisy, mitral endocarditis, and
myocarditis.

This case was one of extreme severity and illustrates a
difficulty that has to be reckoned with in studying chorea.
During the last week of life blebs full of serous fluid developed
upon the back and elsewhere and the incessant movements
rapidly converted them into open sores. An occurrence such
as this must, we readily admit, introduce the question of
secondary infection and increase the difficulties of an accurate
interpretation of any results. For our own part we are
sceptical that, under these conditions, a secondary infection
will explain the results of post-mortem investigation, because
it has been repeatedly demonstrated that in acute rheumatism
similar bacteriological results to those we obtained on this
occasion can be shown when there is no question at all of
open sores.

There is yet another point of interest about this case.
Some eminent bacteriologists dispute any direct association
between the diplococcus and acute rheumatism and some
have failed to find the micrococcus after repeated search in
cases of rheumatism. In this case, however, a pure growth



246 A CONTRIBUTION TO THE

of a diplococcus was obtained from the heart's blood by
Dr. F. H. Thiele, clinical pathologist to University College
Hospital. Its presence was demonstrated in the pericardium by
Dr. T. Lewis, the house plrysician to the case. It was again de-
monstrated by one of us in the pia mater and by another in the
brain, and was cultivated by Dr. Paine, and on experimental
injection into animals produced multiple arthritis and peri-
carditis of the usual type. It will be seen, then, that five
different observers independently recognised the occurrence of
a diplococcus in this case, which had the features of the
diplococcus described in rheumatism.

Pathological investigation. Only the right half of the brain,
brain-stem, and cerebellum and a portion of the diseased heart
valve were received for examination. Macroscopical examina-
tion. The vessels of the meninges and cortex of the hemisphere,
and to a less extent those of the membranes on the base of the
brain and brain-stem, were very much engorged. No exuda-
tion or signs of inflammation were visible to the naked eye, but
several small subpial haemorrhages could be seen on the
convexity of the hemisphere. Microscopical examination.
Sections stained with hematoxylin revealed great congestion
of the blood-vessels of the membranes and of the brain itself,
and in many places small haemorrhages were visible, especially
on the under surface of the pia mater. A small proportion of
the vessels of the pia-arachnoid, generally the smaller arteries,
were thrombosed, especially over the convexity of the hemi-
sphere, and there was in places definite evidence of serous
exudation and small round cell infiltration into the membranes
in the immediate neighbourhood of the vessels. Thrombosed
vessels were still more common in the cortex and subcortical
white matter, but in the majority the clots seemed to be quite
recent, though some were partially organised. Thrombosed
vessels could be occasionally followed into, or found within,
small patches of softening, which lay most frequently in the
deeper layers of the cortex. The destruction of tissue within
them was never complete ; there was considerable serous
exudation into the recent ones, while the older were marked
by proliferation of neuroglial nuclei and sclerosis. There was
also small round cell infiltration into the sheaths and peri-
vascular spaces of many of the vessels which were not throm-
bosed and a polymorphonuclear leucocyte was occasionally seen



PATHOLOGY OF CHOREA 247

among them. These changes were equally marked over the
whole hemisphere and within the basal ganglia, but no foci of
necrosis were observed in the cerebellum, pons, or medulla,
though here, too, there was considerable congestion of the vessels
and frequently small round cell infiltration into their sheaths.
When the brain was examined by Nissl's method definite
cell changes were found, which were greater in the cerebral
cortex than in any other part of the central nervous system.
Practically all the cortical cells were affected ; as a rule they
were swollen and distended, their tigroid had partly disappeared
so that they stained diffusely or occasionally almost uniformly,
and their nuclei, which were swollen and excentrically situated
in a certain number of the cells, stained more deeply than
normal. The nucleoli appeared unaltered and the cell pro-
cesses seemed normal except that they were not easily visible
owing to diminution of their chromatophilic substance. The
degree of affection of the large Betz cells was very variable.
In the majority there was only slight chromatolysis immediately
around the nucleus where the Nissl bodies were broken up
into a deeply staining granular material, while they remained
normal in the periphery of the cell and in the dendrites. In
the next stage there was more extensive perinuclear chroma-
tolysis and the nuclei were more generally swollen and more
frequently excentric. A small number of cells were still
more severely affected ; their outlines were scarcely recognis-
able, their nuclei were shrunken and deformed, and no stain-
able substance was visible in them. The cells of the basal
ganglia were less affected ; there was at the most only evidence
of commencing chromatolysis and slight swelling of the nuclei.
The cells of the different portions of the brain-stem were in
much the same state ; they stained rather faintly and there
was commencing disintegration of their tigroid masses. No
definite changes were recognised in the cells of the cerebellum.
Various portions of the forebrain and brain-stem were treated
by Marc hi 's method. A few degenerated fibres were found on
the borders and neighbourhood of the small patches of soften-
ing, but there was otherwise no evidence of disease in the
cortex except in the presence of dark granular masses in the



Online LibraryF. J. (Frederic John) PoyntonResearches on rheumatism → online text (page 22 of 42)